Giant-Cell Aortitis-Induced Acute Aortic Insufficiency: An Underestimated Etiology

Background

Aortic insufficiency is the third most common valvular pathology in the general population, representing 13% of heart valve disease. It can originate from an intrinsic aortic valve disease (primary), or from pathological changes in the aortic root (secondary) [1].

This clinical entity can be acute or chronic. Acute aortic insufficiency is characterized by a sudden increase in left ventricular end-diastolic volume, with the left ventricular chamber unable to accommodate the abrupt change in volume. It can be secondary to multiple conditions, including infective endocarditis, aortic root pathologies (eg, dissection, aortitis), or traumatic injury. In contrast, chronic aortic insufficiency is most commonly caused by atherosclerotic valve degeneration and congenital bicuspid aortic valve [2]. Aortitis involves a broad spectrum of disorders characterized by inflammatory changes in the aortic wall. This pathology can be subsequently classified depending on its etiology into inflammatory and infectious causes. Large-vessel vasculitis (giant-cell arteritis, Takayasu arteritis, and IgG4-related aortitis) is the most common non-infectious causes of aortitis, whereas syphilis and bacterial and mycobacterial infectious are the most common infectious etiologies worldwide [3].

GCA is a classic systemic rheumatic disease of older adults; it rarely occurs in individuals younger than 50 years of age and peaks in incidence in the seventh decade of life. It mainly involves the large- and medium-sized arteries and can produce a wide spectrum of clinical manifestations. At one end of the spectrum are patients with cranial manifestations who typically have a positive temporal artery biopsy. At the other end are patients with predominantly large-vessel involvement, who frequently lack cranial manifestations, and whose symptoms are often subtle and nonspecific. These patients typically have a negative temporal artery biopsy and require large-vessel imaging to confirm the diagnosis. Finally, some patients have overlapping features of cranial manifestations and large-vessel disease. Therefore, clinicians should have a high index of suspicion, since this pathology can evolve into potentially life-threatening conditions, including aortic aneurysm, aortic wall rupture, and aortic acute dissection [4].

Here, we present a case of a 76-year-old woman who presented to the ED with symptoms consistent with heart failure and she was found to have an aortic insufficiency secondary to giant-cell aortitis.

Case Report

A 76-year-old woman with no significant past medical history presented to the Emergency Department (ED) with shortness of breath for 3 days. She described her shortness of breath as gradual in onset, and progressive, which aggravated with exertion and alleviated with rest. It was associated with orthopnea, paroxysmal nocturnal dyspnea, and mild productive cough with white sputum. The patient denied any fever, chest pain, palpitation, headache, nausea, vomiting, abdominal pain, joint pain, or urinary or bowel habits changes. She was a former smoker and quit smoking 5 years before. She never had similar symptoms before.

On arrival at the ED, she was hypotensive, tachypneic, and hypoxemic, with a blood pressure of 92/41 mmHg, respiratory rate of 55 per minute, and oxygen saturation of 85% on room air. Physical examination was significant for jugular venous distension up to the angle of the mandible, loud but short diastolic murmur at the right upper sternal border, and 2+ pitting edema in bilateral lower extremities. An electrocardiogram (EKG) showed sinus tachycardia with nonspecific ST-T wave changes in lateral leads. A chest X-ray showed perihilar and bibasilar opacities bilaterally. Laboratory studies were significant for elevated brain natriuretic peptide (BNP) 593 [<100 pg/ml], and D-dimer 482 [0–230 ng/ml]. Arterial blood gas analysis showed mixed respiratory and metabolic acidosis, pH 7.00 (7.35–7.45), PCO2 61 (35–45 mmHg), and HC03 11.6 (22–26 mmol/L).

An initial diagnosis of acute decompensated heart failure was made, and intravenous furosemide was started. The patient was placed on BiPAP and was transferred to the Intensive Care Unit (ICU) for further management. A transthoracic echocardiogram (TTE) demonstrated LVEF of 25–30%, dilated left ventricle, and moderate-to-severe aortic insufficiency (AI). Wall motion abnormality was also noted at the anteroapical segment. To rule out aortic dissection as an acute cause of AI, the decision was made to perform a transesophageal echocardiography (TEE), as the patient was too unstable to be transferred for computed tomography (CT) angiography. TEE demonstrated LVEF 30–35% and dilated ascending aorta measuring 4.6 cm with severe aortic insufficiency and absence of dissection flap (Figure 1). Continuous-wave Doppler imaging across the aortic valve demonstrated severe AI with p1/2 time 97 ms (Figure 2). Cardiac catheterization revealed mild non-obstructive coronary arteries. It also showed moderate-to-severe aortic regurgitation. CT angiography also showed evidence of a large ascending and aortic root aneurysm measuring 4.6 cm in diameter (Figure 3).

The patient was started on dobutamine and Levophed and was transferred to another facility for cardiothoracic surgery. During surgery, she was noted to have a large aortic root aneurysm with a trileaflet aortic valve with thickened retracted aortic valve leaflets. There was also a prolapse of the left and the non-coronary cusp. The annulus was then debrided back to healthy tissue and the aortic valve leaflets were removed. Ethibond pledged sutures were placed in the supra-annular position and they were brought sequentially through a 23-mm composite valve conduit. The sutures were then tied down. Coronary buttons were cut from surrounding aortic tissue and then re-implanted. The histopathology of the portion of the aorta showed medial necrosis surrounded by dense lymphocytic and histiocytic inflammation. Inset demonstrated multi-nucleate giant cells (Figure 4). Given the patient’s age, clinical presentation, and histopathology findings, the diagnosis of giant-cell aortitis was made. An elevated ESR of 57 further supported the diagnosis of vasculitis. A rheumatologist was consulted, and after clearance from cardiothoracic surgery and appropriate cardiac rehabilitation, the patient was started on steroids and safely discharged home. One week later, she was seen in an outpatient clinic and her symptoms had significantly improved. She will continue to follow up with rheumatology for further management of GCA.

Discussion

AI, also called aortic regurgitation (AR), can be acute or chronic in presentation. Acute aortic insufficiency is considered a medical emergency due to the inability of the left ventricle to quickly overcome the increase in left ventricular end-diastolic pressure (LVEDP) and volume.

The sudden increase in LVEDP can result in mitral regurgitation and eventually cause pulmonary vascular congestion and edema. With no intervention, this condition can progress to decreased cardiac output and cardiogenic shock. This explains the presentation of our patient and the need for emergent surgery. Etiologies, clinical presentations, and management are distinct in acute and chronic AI [5].

Primary causes of AR can be either aortic valve (AV) leaflet diseases or aortic root and ascending aorta pathologies. Acute leaflet abnormalities include infective endocarditis, traumatic rupture, acute prosthetic valve dysfunction, and post-aortic balloon valvoplasty. Acute ascending or root abnormalities include acute aortic dissection, perivalvular leak or dehiscence of the prosthetic valve, and, less frequently, aortitis [5].

Acute AI usually presents with pulmonary edema, with other signs and symptoms of underlying causes like endocarditis or aortic dissection. However, in fewer cases, new-onset aortic regurgitation might be the only clue to impending failure, and diagnosis in the initial stages can be challenging. Pulse pressure is often normal or slightly widened in acute AI as compared to chronic AI, the same as the normal point of maximal left ventricular (LV) impulse acute settings.

Diagnosis can be confirmed with echocardiography, which can identify endocarditis and dissection if present, with the highest sensitivity and specificity with TEE. Computed tomography (CT) is the preferred imaging modality, especially in unstable patients, to localize the potential flap and evaluate the anatomy [6]. The treatment of acute severe AR is emergent surgery, especially in hemodynamically unstable patients. Medical management to stabilize the patient consists of positive inotropes and vasodilators, which should be adjusted based on the arterial pressure. Beta-blockers should be avoided in acute AR, even in the presence of aortic dissection, which can drop the cardiac output by decreasing the compensatory tachycardia in this setting [7].

As discussed earlier, one of the rare causes of acute aortic insufficiency is aortitis, which can have infectious (eg, syphilis, mycobacterial, or mycotic) or inflammatory etiologies. Inflammatory aortitis can be idiopathic or a part of systemic inflammatory diseases like giant-cell arteritis (Horton’s disease), Bechet’s disease, Takayasu’s arteritis, IgG-4 related disease, and sarcoidosis, among others [8,9]. Histological findings range from necrosis and inflammation to fibrosis and regenerative changes. In the acute phase, the inflammatory changes can be seen in all 3 layers, with lymphocytic, lymphoplasmacytic, and fibroblast infiltration, whereas in the chronic phase, the aorta is fibrotic in all 3 layers, with loose elastic tissue [10].

Inflammatory aortitis accounts for a very small percentage of the patients presenting with acute heart failure. In case of ascending aorta involvement, aortic regurgitation and later aneurysmal dilation and dissection can occur [11].

Giant-cell arteritis is a granulomatosis inflammatory disease affecting medium-sized and large arteries in patients over age 50 years. In the majority of the cases, it involves the temporal arteries, ophthalmic, occipital, and vertebral arteries; however, the aorta is affected in only 14% of cases [12]. Its diagnosis should be suspected in any patient above 50 years of age, especially in the setting of elevated ESR/CRP with any sign or symptoms of new-onset headache, jaw claudications, vision changes, constitutional symptoms, or any sign/symptoms of vascular abnormalities. Most patients with giant-cell (GC) aortitis are diagnosed postoperatively based on the pathology results and have no prior diagnosis of inflammatory diseases. Hence, a high mortality rate (2-week mortality of 80%) and 46% dissection have been reported in these cases [12]. Clinical presentation can range from asymptomatic disease to hypertension, aneurysmal rupture, or spontaneous dissection, which can be fatal.

In a cohort study conducted by Gagné-Loranger et al on 40 patients with GC aortitis, among 40 patients with confirmed giant-cell aortitis based on pathology results, only 22.5% of patients had a previous history of polymyalgia rheumatica or temporal arteritis [13]. A similar finding is reported by Zehr et al in another series of 37 patients, where most of the patients had symptoms related to aneurysmal dilatation or aortic regurgitation without previous suspicion of inflammatory disease [14]. Similarly, in this case report, we describe a patient with no previous diagnosis of inflammatory disease, who presented with acute pulmonary edema and severe aortic regurgitation during the physical examination, which resulted in an acute GC aortitis diagnosis.

In a recently published retrospective study by Espitia et al on 171 patients who were diagnosed with GC arteritis between 1989 to 2019, the thoracic aortic aneurysm was detected in 23.6% and aortic dissection in 5% of the patients. Aortitis was symptomatic in 55 cases (32%), including 51% with chest pain, 31% with abdominal pain, 16% with back pain, and 35% had recent dyspnea with previously unknown aortic insufficiency. Risk factor reviews demonstrated that symptomatic aortitis was significantly more common in patients with cardiovascular risk factors like smoking and hypertension [15].

Based on the literature review as described above, inflammatory aortitis is a very rare cause of acute aortic insufficiency, and most of the time diagnosis is challenging secondary to low clinical suspicion and no previous confirmed inflammatory diagnosis. In patients with new-onset aortic regurgitation, in addition to acute management, aortitis should be included in the differential diagnosis, which requires extensive rheumatologic and immunologic evaluation.

Conclusions

In this article, we present a case of giant-cell aortitis as an unusual etiology of acute aortic insufficiency, which is most probably under-detected in clinical practice. Searching for a cause after the acute event may provide the background diagnosis, which contributes to the long-term survival of patients with aortitis. In addition to describing the case, we aim to highlight the importance of proper ascending aorta evaluation in patients presenting with new-onset aortic regurgitation and heart failure.